Glycogen synthase kinase 3beta induces apoptosis in cancer cells through increase of survivin nuclear localization.
Glycogen synthase kinase 3beta induces apoptosis in cancer cells through increase of survivin nuclear localization.
复制标题
DOI：
10.1016/j.canlet.2008.06.032
复制
发表时间：
2008-12-08
期刊：
影响因子：
9.7
通讯作者：
Zhou, Muxiang
中科院分区：
文献类型：
--
作者：
Li, Jiansha;Xing, Mingyou;Zhu, Min;Wang, Xi;Wang, Manxiang;Zhou, Sheng;Li, Naping;Wu, Renliang;Zhou, Muxiang
糖原合成酶激酶3β (GSK3β)调节多种信号通路，控制广泛的细胞过程，包括细胞增殖、分化、凋亡和代谢。我们报道了GSK3β的新功能：它与凋亡抑制蛋白（IAP） survivin相互作用，调节其表达，从而调节人肺癌细胞的凋亡。共免疫沉淀实验显示GSK3β可以结合survivin。GSK3β的激活诱导存活素从细胞质转位到细胞核，导致G1细胞周期阻滞和凋亡，以及对化疗药物阿霉素的致敏。相比之下，通过转染显性阴性突变抑制剂DN-GSK3β或选择性抑制剂LiCl使GSK3β失活，可增加细胞质survivin的表达，导致细胞周期的进展和对凋亡的抵抗。这些结果确定了GSK3β在癌细胞中的促凋亡作用，通过其在亚细胞再分配中对生存素的调节。这一新的作用表明，GSK3β有可能通过药理激活来加强对癌症患者的治疗，包括那些有耐药性的癌症患者。
Glycogen synthase kinase 3β (GSK3β) regulates numerous signaling pathways that control a wide range of cellular processes, including cell proliferation, differentiation, apoptosis and metabolism. We report a novel function of GSK3β: It interacts with the inhibitor-of-apoptosis protein (IAP) survivin to modulate its expression, thus regulating apoptosis in human lung cancer cells. A co-immunoprecipitation assay revealed that GSK3β can bind survivin. Activation of GSK3β induced translocation of survivin from the cytoplasm to the nucleus, resulting in G1 cell-cycle arrest and apoptosis, as well as sensitization to the chemotherapeutic drug doxorubicin. In contrast, inactivation of GSK3β, either by transfection of a dominant-negative mutant inhibitor DN-GSK3β or with selective inhibitor LiCl, increased cytoplasmic survivin expression, leading to cell cycle progression and resistance to apoptosis. These results identify a pro-apoptotic role for GSK3β in cancer cells, through its modulation of survivin in subcellular redistribution. This new role suggests that there is a potential for pharmacologic activation of GSK3β to enhance treatment of cancer patients, including those with resistance.
登录
查看更多内容
影响因子：
8.8
作者：
Grabowski, P;Kühnel, T;Mühr-Wilkenshoff, F;Heine, B;Stein, H;Höpfner, M;Germer, CT;Scherübl, H
通讯作者：
Scherübl, H
影响因子：
4.8
作者：
Connell, Claire M.;Colnaghi, Rita;Wheatley, Sally P.
通讯作者：
Wheatley, Sally P.
影响因子：
9.7
作者：
Temme, Achim;Rodriguez, Jose A.;Rieber, E. Peter
通讯作者：
Rieber, E. Peter
影响因子：
7.7
作者：
Knauer, Shirley K.;Bier, Carolin;Stauber, Roland H.
通讯作者：
Stauber, Roland H.
DOI：
10.1016/j.bbrc.2005.07.041
发表时间：
2005-09-09
影响因子：
3.1
作者：
Shakoori, A;Ougolkov, A;Minamoto, T
通讯作者：
Minamoto, T